Combination Vaccine Immunotherapy (DRibbles) for Patients With Definitively-Treated Stage III Non-small Cell Lung Cancer

UbiVac

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Cyclophosphamide; Drug: Imiquimod; Biological: HPV vaccine; Drug: GM-CSF; Biological: DRibble vaccine

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01909752

R44CA121612 (U.S. NIH Grant/Contract)

UbiVac DPV-001

Details and patient eligibility

About

This study will test an investigational vaccine, called DRibbles, for the treatment of non-small cell lung cancer (NSCLC). We hypothesize that vaccination with the DRibble vaccine will cause an immune responses against proteins contained in the DRibble vaccine and the protein antigens targeted by this strong immune response will include common antigens shared by both the vaccine and the patient's tumor.

Full description

This is an open-label, randomized study in which the first 33 patients will be assigned to receive the either:

• DRibbles vaccine and HPV vaccine
• DRibbles vaccine, HPV vaccine, and imiquimod
• DRibbles vaccine, HPV vaccine, and GM-CSF After 11 patients have been assigned to each group, the study arm with the greatest number of vaccine-induced strong antibody responses will then continue with enrollment of 15 further patients. The primary objective is to determine the best strategy to induce strong (>15 fold) tumor-specific or tumor-associated antibody responses in patients with stage III A and B NSCLC. The goal is to select one regimen to advance to additional clinical trials.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Stage IIIA or IIIB histologically proven non-small cell lung cancer
• Completion of definitive therapy
• Enrollment from 28 days to 12 weeks from completion of definitive therapy
• Toxicities from definitive therapy resolved to less than grade 1
• ECOG performance status 0-1
• Negative pregnancy test in women of childbearing potential
• Agree to avoid pregnancy or fathering a child while on study treatment
• Ability to give informed consent and comply with protocol
• Anticipated survival minimum of 6 months
• Prior therapy with investigational agents must be completed at least 3 weeks prior to study enrollment
• Normal organ and marrow function as defined by specific lab tests
• Archived tumor tissue available

Exclusion criteria

• Active autoimmune disease except for vitilogo or hypothyroidism
• Active other malignancy
• Known HIV+ and/or Hepatitis B or C positive
• Medical or psychiatric conditions that would preclude safe participation
• Ongoing chemotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

DRibble Vaccine Alone

Experimental group

Description:

Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations.

Treatment:

Biological: HPV vaccine

Biological: DRibble vaccine

Drug: Cyclophosphamide

DRibble vaccine with imiquimod

Experimental group

Description:

Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. Imiquimod cream (5%, 250 mg containing 12.5 mg imiquimod - one packet/day) will be self applied once per day starting with the second vaccine (week 4) and for four days following each vaccine cycle. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations.

Treatment:

Biological: HPV vaccine

Drug: Imiquimod

Biological: DRibble vaccine

Drug: Cyclophosphamide

DRibble vaccine with GM-CSF

Experimental group

Description:

Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. GM-CSF will be administered at 50 mcg/day starting with the second vaccine (week 4) and continuing with each subsequent vaccine. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations.

Treatment:

Drug: GM-CSF

Biological: HPV vaccine

Biological: DRibble vaccine

Drug: Cyclophosphamide